Jeffrey Miller
University of Minnesota, MN·Microbiology & Immunology
Natural killer (NK) cells are immune cells that can recognize and destroy cancer cells without prior training. Infusing donor NK cells into patients has produced remissions in some blood cancers.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biomedical Engineering
- Topics
natural killer cells
NK cells
iPSC
- Grants
- 5 known grants, through Jul 2030
What they work on
- Engineer iPSC-derived NK (iNK) cells with gene edits that improve homing and migration into tumors, tolerance of low oxygen (hypoxia), and survival after transfer into patients with solid tumors.
- Test iNK cells carrying a chimeric antigen receptor (CAR) built from a camelid nanobody against B7-H3, a protein found on glioblastoma and prostate cancer but not on normal tissues, and compare them with iPSC-derived T cells carrying the same CAR.
- Conduct a multi-institutional phase I/II trial of donor adaptive NK cells, induced by cytomegalovirus (CMV) and marked by the NKG2C receptor, for patients with AML or myelodysplastic syndrome.
- Test whether delivering IL-15 through tri-specific killer engagers (TriKEs), three-part engineered proteins linking NK cells to tumor cells, limits unwanted activation of patients' CD8+ T cells.
- Clinically test an iNK product with a CD19-targeting CAR, CD16 and membrane-bound IL-15 in non-Hodgkin lymphoma, and test preclinically whether altering NK cell metabolism improves performance in the body.
- Run a phase I trial of FT516 iNK cells, which carry a CD16 receptor that cannot be cleaved off, delivered into the abdominal cavity of ovarian cancer patients, and test combinations with TriKEs and a CD64/16A receptor iNK product.
- Test in a phase I trial whether giving daratumumab, an anti-CD38 antibody, before FT538 iNK cells (high-affinity CD16, IL-15 fusion, CD38 knockout) improves iNK persistence and killing of AML cells.
- Optimize IL-15 signaling in CD38-knockout iNK cells, and test an anti-CD5 antibody-drug conjugate as a safer way to clear the patient's immune cells before infusion.
- Test whether targeting two tumor antigens at once, through a CAR plus CD16-engaging TriKEs, increases how well iNK cells kill acute myeloid leukemia.
More about the research
But cells taken from individual donors vary from batch to batch, are hard to gene-edit, and are expensive to make. They are also difficult to ship beyond specialty centers. The research described here aims to replace donor cells with "off-the-shelf" NK cells grown from induced pluripotent stem cells (iPSCs), which are stem cells reprogrammed from adult cells that can become almost any cell type. Because these iNK cells come from one engineered source, they can be gene-edited, made in many doses, and given repeatedly. The projects test these cells against leukemia, lymphoma, ovarian cancer, brain tumors and prostate cancer, often combined with engineered proteins that steer NK cells toward tumors. The PI also co-leads the Immunology Program of the Masonic Cancer Center, which is one of the grants listed.
Why it matters
Patients with relapsed acute myeloid leukemia, non-Hodgkin lymphoma, ovarian cancer, glioblastoma and prostate cancer could benefit from immune cell therapies that are mass-produced, gene-edited, and stored frozen until needed. Such products could be shipped to hospitals beyond specialty centers and given in repeated doses. They could also lower the cost and variability that limit treatments made from individual donors' cells.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Wagner
University of Minnesota, MN·Medicine & Clinical Research
Establish the safety and maximum tolerated dose of donor CAR19 regulatory T cells, given with and without IL-2, in patients with relapsed or refractory CD19+ acute lymphocytic leukemia, measuring cell persistence and tumor killing.
Peter Chockley
Ohio State University, OH·Microbiology & Immunology·Early-career
Develop monomeric chimeric antigen receptors (single-unit CARs with a stable off state) for natural killer cells, adding immune synapse augmentation, to reduce erratic signaling and improve killing of pediatric solid tumor cells.
Dan Kaufman
University of California-San Diego, CA·Microbiology & Immunology
Test whether virus-like particles carrying DARPin or scFv targeting proteins deliver mRNA selectively to T cells, NK cells or macrophages, first in cell lines and then in primary human immune cells.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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